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1.
  • Abdallah, J., et al. (author)
  • Study of double-tagged gamma gamma events at LEPII
  • 2006
  • In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 46:3, s. 559-568
  • Journal article (peer-reviewed)abstract
    • Double-tagged interactions of photons with virtualities Q(2) between 10 GeV2 and 200 GeV2 are studied with the data collected by DELPHI at LEPII from 1998 to 2000, corresponding to an integrated luminosity of 550 pb(-1). The gamma*gamma* -> mu(+)mu(-) data agree with QED predictions. The cross-section of the reaction gamma*gamma* -> hadrons is measured and compared to the LO and NLO BFKL calculations.
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3.
  • Spronk, H. M. H., et al. (author)
  • Atherothrombosis and Thromboembolism : Position Paper from the Second Maastricht Consensus Conference on Thrombosis
  • 2018
  • In: Thrombosis and Haemostasis. - : SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN. - 0340-6245 .- 2567-689X. ; 118:2, s. 229-250
  • Research review (peer-reviewed)abstract
    • Atherothrombosis is a leading cause of cardiovascular mortality and long-term morbidity. Platelets and coagulation proteases, interacting with circulating cells and in different vascular beds, modify several complex pathologies including atherosclerosis. In the second Maastricht Consensus Conference on Thrombosis, this theme was addressed by diverse scientists from bench to bedside. All presentations were discussed with audience members and the results of these discussions were incorporated in the final document that presents a state-of-the-art reflection of expert opinions and consensus recommendations regarding the following five topics:1. Risk factors, biomarkers and plaque instability: In atherothrombosis research, more focus on the contribution of specific risk factors like ectopic fat needs to be considered; definitions of atherothrombosis are important distinguishing different phases of disease, including plaque (in) stability; proteomic and metabolomics data are to be added to genetic information.2. Circulating cells including platelets and atherothrombosis: Mechanisms of leukocyte and macrophage plasticity, migration, and transformation in murine atherosclerosis need to be considered; diseasemechanism-based biomarkers need to be identified; experimental systems are needed that incorporatewhole-blood flow to understand how red blood cells influence thrombus formation and stability; knowledge on platelet heterogeneity and priming conditions needs to be translated toward the in vivo situation.3. Coagulation proteases, fibrin(ogen) and thrombus formation: The role of factor (F) XI in thrombosis including the lower margins of this factor related to safe and effective antithrombotic therapy needs to be established; FXI is a key regulator in linking platelets, thrombin generation, and inflammatory mechanisms in a renin-angiotensin dependent manner; however, the impact on thrombin-dependent PAR signaling needs further study; the fundamental mechanisms in FXIII biology and biochemistry and its impact on thrombus biophysical characteristics need to be explored; the interactions of red cells and fibrin formation and its consequences for thrombus formation and lysis need to be addressed. Platelet-fibrin interactions are pivotal determinants of clot formation and stability with potential therapeutic consequences.4. Preventive and acute treatment of atherothrombosis and arterial embolism; novel ways and tailoring? The role of protease-activated receptor (PAR)-4 vis a vis PAR-1 as target for antithrombotic therapy merits study; ongoing trials on platelet function test-based antiplatelet therapy adjustment support development of practically feasible tests; risk scores for patients with atrial fibrillation need refinement, taking new biomarkers including coagulation into account; risk scores that consider organ system differences in bleeding may have added value; all forms of oral anticoagulant treatment require better organization, including education and emergency access; laboratory testing still needs rapidly available sensitive tests with short turnaround time.5. Pleiotropy of coagulation proteases, thrombus resolution and ischaemia-reperfusion: Biobanks specifically for thrombus storage and analysis are needed; further studies on novelmodified activated protein C-based agents are required including its cytoprotective properties; new avenues for optimizing treatment of patients with ischaemic stroke are needed, also including novel agents that modify fibrinolytic activity (aimed at plasminogen activator inhibitor-1 and thrombin activatable fibrinolysis inhibitor.
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4.
  • Grieser, M., et al. (author)
  • Storage ring at HIE-ISOLDE Technical design report
  • 2012
  • In: The European Physical Journal Special Topics. - : Springer Science and Business Media LLC. - 1951-6355 .- 1951-6401. ; 207:1, s. 1-117
  • Research review (peer-reviewed)abstract
    • We propose to install a storage ring at an ISOL-type radioactive beam facility for the first time. Specifically, we intend to setup the heavy-ion, low-energy ring TSR at the HIE-ISOLDE facility in CERN, Geneva. Such a facility will provide a capability for experiments with stored secondary beams that is unique in the world. The envisaged physics programme is rich and varied, spanning from investigations of nuclear ground-state properties and reaction studies of astrophysical relevance, to investigations with highly-charged ions and pure isomeric beams. The TSR might also be employed for removal of isobaric contaminants from stored ion beams and for systematic studies within the neutrino beam programme. In addition to experiments performed using beams recirculating within the ring, cooled beams can also be extracted and exploited by external spectrometers for high-precision measurements. The existing TSR, which is presently in operation at the Max-Planck Institute for Nuclear Physics in Heidelberg, is well-suited and can be employed for this purpose. The physics cases as well as technical details of the existing ring facility and of the beam and infrastructure requirements at HIE-ISOLDE are discussed in the present technical design report.
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5.
  • Schulze, S., et al. (author)
  • GRB 120422A/SN 2012bz : Bridging the gap between low- and high-luminosity gamma-ray bursts
  • 2014
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 566
  • Journal article (peer-reviewed)abstract
    • Context. At low redshift, a handful of gamma-ray bursts (GRBs) have been discovered with luminosities that are substantially lower (L-iso less than or similar to 10(48.5) erg s(-1)) than the average of more distant ones (L-iso greater than or similar to 10(49.5) erg s(-1)). It has been suggested that the properties of several low-luminosity (low-L) GRBs are due to shock break-out, as opposed to the emission from ultrarelativistic jets. This has led to much debate about how the populations are connected. Aims. The burst at redshift z = 0.283 from 2012 April 22 is one of the very few examples of intermediate-L GRBs with a gamma-ray luminosity of L-iso similar to 10(49.6-49.9) erg s(-1) that have been detected up to now. With the robust detection of its accompanying supernova SN 2012bz, it has the potential to answer important questions on the origin of low-and high-L GRBs and the GRB-SN connection. Methods. We carried out a spectroscopy campaign using medium-and low-resolution spectrographs with 6-10-m class telescopes, which covered a time span of 37.3 days, and a multi-wavelength imaging campaign, which ranged from radio to X-ray energies over a duration of similar to 270 days. Furthermore, we used a tuneable filter that is centred at H alpha to map star-formation in the host and the surrounding galaxies. We used these data to extract and model the properties of different radiation components and fitted the spectral energy distribution to extract the properties of the host galaxy. Results. Modelling the light curve and spectral energy distribution from the radio to the X-rays revealed that the blast wave expanded with an initial Lorentz factor of Gamma(0) similar to 50, which is a low value in comparison to high-L GRBs, and that the afterglow had an exceptionally low peak luminosity density of less than or similar to 2 x 10(30) erg s(-1) Hz(-1) in the sub-mm. Because of the weak afterglow component, we were able to recover the signature of a shock break-out in an event that was not a genuine low-L GRB for the first time. At 1.4 hr after the burst, the stellar envelope had a blackbody temperature of k(B)T similar to 16 eV and a radius of similar to 7 x 10(13) cm (both in the observer frame). The accompanying SN 2012bz reached a peak luminosity of M-V = -19.7 mag, which is 0.3 mag more luminous than SN 1998bw. The synthesised nickel mass of 0.58 M-circle dot, ejecta mass of 5.87 M-circle dot, and kinetic energy of 4.10x10(52) erg were among the highest for GRB-SNe, which makes it the most luminous spectroscopically confirmed SN to date. Nebular emission lines at the GRB location were visible, which extend from the galaxy nucleus to the explosion site. The host and the explosion site had close-to-solar metallicity. The burst occurred in an isolated star-forming region with an SFR that is 1/10 of that in the galaxy's nucleus. Conclusions. While the prompt gamma-ray emission points to a high-L GRB, the weak afterglow and the low Gamma(0) were very atypical for such a burst. Moreover, the detection of the shock break-out signature is a new quality for high-L GRBs. So far, shock break-outs were exclusively detected for low-L GRBs, while GRB 120422A had an intermediate L-iso of similar to 10(49.6-49.9) erg s(-1). Therefore, we conclude that GRB 120422A was a transition object between low-and high-L GRBs, which supports the failed-jet model that connects low-L GRBs that are driven by shock break-outs and high-L GRBs that are powered by ultra-relativistic jets.
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6.
  • Grieser, M., et al. (author)
  • Storage ring at HIE-ISOLDE
  • 2012
  • In: European Physical Journal: Special Topics. - : Springer Science and Business Media LLC. - 1951-6401 .- 1951-6355. ; 207:1, s. 1-117
  • Journal article (peer-reviewed)abstract
    • We propose to install a storage ring at an ISOL-type radioactive beam facility for the first time. Specifically, we intend to setup the heavy-ion, low-energy ring TSR at the HIE-ISOLDE facility in CERN, Geneva. Such a facility will provide a capability for experiments with stored secondary beams that is unique in the world. The envisaged physics programme is rich and varied, spanning from investigations of nuclear ground-state properties and reaction studies of astrophysical relevance, to investigations with highly-charged ions and pure isomeric beams. The TSR might also be employed for removal of isobaric contaminants from stored ion beams and for systematic studies within the neutrino beam programme. In addition to experiments performed using beams recirculating within the ring, cooled beams can also be extracted and exploited by external spectrometers for high-precision measurements. The existing TSR, which is presently in operation at the Max-Planck Institute for Nuclear Physics in Heidelberg, is well-suited and can be employed for this purpose. The physics cases as well as technical details of the existing ring facility and of the beam and infrastructure requirements at HIE-ISOLDE are discussed in the present technical design report.
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7.
  • Erlinge, David, et al. (author)
  • Reduction in platelet reactivity with prasugrel 5 mg in low-body-weight patients is noninferior to prasugrel 10 mg in higher-body-weight patients
  • 2012
  • In: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 60:20, s. 2032-2040
  • Journal article (peer-reviewed)abstract
    • Objectives: The aim of this study was to confirm prior modeling data suggesting that prasugrel 5 mg in low-body-weight (LBW) patients would be noninferior to prasugrel 10 mg in higher-body-weight (HBW) patients as assessed by maximal platelet aggregation (MPA). Background: Prasugrel 10 mg reduced ischemic events compared with clopidogrel 75 mg but increased bleeding, particularly in LBW patients. Methods: In this blinded, 3-period, crossover study in stable patients with coronary artery disease (CAD) taking aspirin, prasugrel 5 and 10 mg and clopidogrel 75 mg were administered to LBW (56.4 ± 3.7 kg; n = 34) and HBW patients (84.7 ± 14.9 kg; n = 38). Assays included light transmission aggregometry (LTA), VerifyNow P2Y12 (VN), and vasodilator-associated stimulated phosphoprotein (VASP) level measured predose and after each 12-day treatment. Results: Median MPA by LTA for prasugrel 5 mg in LBW patients was noninferior to the 75th percentile for prasugrel 10 mg in HBW patients (primary endpoint) and mean MPA was similar, but active metabolite exposure was lowered by 38%. Within LBW patients, prasugrel 5 mg lowered MPA more than clopidogrel (least squares mean difference [95% confidence interval]: -3.7% [-6.72%, -0.69%]) and resulted in lower rates of high on-treatment platelet reactivity (HPR). Within HBW patients, prasugrel 10 mg lowered MPA more than clopidogrel (-16.9% [-22.3%, -11.5%]). Similar results were observed by VN and VASP. Prasugrel 10 mg in LBW patients was associated with more mild to moderate bleeding (mainly bruising) compared with prasugrel 5 mg and clopidogrel. Conclusions: In aspirin-treated patients with CAD, prasugrel 5 mg in LBW patients reduced platelet reactivity to a similar extent as prasugrel 10 mg in HBW patients and resulted in greater platelet inhibition, lower HPR, and similar bleeding rates compared with clopidogrel. (Comparison of Prasugrel and Clopidogrel in Low Body Weight Versus Higher Body Weight With Coronary Artery Disease [FEATHER]; NCT01107925)
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8.
  • Ho, Anna Y. Q., et al. (author)
  • A Search for Extragalactic Fast Blue Optical Transients in ZTF and the Rate of AT2018cow-like Transients
  • 2023
  • In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 949:2
  • Journal article (peer-reviewed)abstract
    • We present a search for extragalactic fast blue optical transients (FBOTs) during Phase I of the Zwicky Transient Facility (ZTF). We identify 38 candidates with durations above half-maximum light 1 day < t (1/2) < 12 days, of which 28 have blue (g - r less than or similar to -0.2 mag) colors at peak light. Of the 38 transients (28 FBOTs), 19 (13) can be spectroscopically classified as core-collapse supernovae (SNe): 11 (8) H- or He-rich (Type II/IIb/Ib) SNe, 6 (4) interacting (Type IIn/Ibn) SNe, and 2 (1) H&He-poor (Type Ic/Ic-BL) SNe. Two FBOTs (published previously) had predominantly featureless spectra and luminous radio emission: AT2018lug (The Koala) and AT2020xnd (The Camel). Seven (five) did not have a definitive classification: AT 2020bdh showed tentative broad H alpha in emission, and AT 2020bot showed unidentified broad features and was 10 kpc offset from the center of an early-type galaxy. Ten (eight) have no spectroscopic observations or redshift measurements. We present multiwavelength (radio, millimeter, and/or X-ray) observations for five FBOTs (three Type Ibn, one Type IIn/Ibn, one Type IIb). Additionally, we search radio-survey (VLA and ASKAP) data to set limits on the presence of radio emission for 24 of the transients. All X-ray and radio observations resulted in nondetections; we rule out AT2018cow-like X-ray and radio behavior for five FBOTs and more luminous emission (such as that seen in the Camel) for four additional FBOTs. We conclude that exotic transients similar to AT2018cow, the Koala, and the Camel represent a rare subset of FBOTs and use ZTF's SN classification experiments to measure the rate to be at most 0.1% of the local core-collapse SN rate.
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9.
  • Lestinsky, M., et al. (author)
  • Physics book: CRYRING@ESR
  • 2016
  • In: European Physical Journal: Special Topics. - : Springer Science and Business Media LLC. - 1951-6401 .- 1951-6355. ; 225:5, s. 797-882
  • Research review (peer-reviewed)abstract
    • The exploration of the unique properties of stored and cooled beams of highly-charged ions as provided by heavy-ion storage rings has opened novel and fascinating research opportunities in the realm of atomic and nuclear physics research. Since the late 1980s, pioneering work has been performed at the CRYRING at Stockholm (Abrahamsson et al. 1993) and at the Test Storage Ring (TSR) at Heidelberg (Baumann et al. 1988). For the heaviest ions in the highest charge-states, a real quantum jump was achieved in the early 1990s by the commissioning of the Experimental Storage Ring (ESR) at GSI Helmholtzzentrum für Schwerionenforschung (GSI) in Darmstadt (Franzke 1987) where challenging experiments on the electron dynamics in the strong field regime as well as nuclear physics studies on exotic nuclei and at the borderline to atomic physics were performed. Meanwhile also at Lanzhou a heavy-ion storage ring has been taken in operation, exploiting the unique research opportunities in particular for medium-heavy ions and exotic nuclei (Xia et al. 2002).
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12.
  • Seiler, Roland, et al. (author)
  • Impact of Molecular Subtypes in Muscle-invasive Bladder Cancer on Predicting Response and Survival after Neoadjuvant Chemotherapy
  • 2017
  • In: European Urology. - : Elsevier BV. - 0302-2838. ; 72:4, s. 544-554
  • Journal article (peer-reviewed)abstract
    • Background: An early report on the molecular subtyping of muscle-invasive bladder cancer (MIBC) by gene expression suggested that response to neoadjuvant chemotherapy (NAC) varies by subtype. Objective: To investigate the ability of molecular subtypes to predict pathological downstaging and survival after NAC. Design, setting, and participants: Whole transcriptome profiling was performed on pre-NAC transurethral resection specimens from 343 patients with MIBC. Samples were classified according to four published molecular subtyping methods. We developed a single-sample genomic subtyping classifier (GSC) to predict consensus subtypes (claudin-low, basal, luminal-infiltrated and luminal) with highest clinical impact in the context of NAC. Overall survival (OS) according to subtype was analyzed and compared with OS in 476 non-NAC cases (published datasets). Intervention: Gene expression analysis was used to assign subtypes. Outcome measurements and statistical analysis: Receiver-operating characteristics were used to determine the accuracy of GSC. The effect of GSC on survival was estimated by Cox proportional hazard regression models. Results and limitations: The models generated subtype calls in expected ratios with high concordance across subtyping methods. GSC was able to predict four consensus molecular subtypes with high accuracy (73%), and clinical significance of the predicted consensus subtypes could be validated in independent NAC and non-NAC datasets. Luminal tumors had the best OS with and without NAC. Claudin-low tumors were associated with poor OS irrespective of treatment regimen. Basal tumors showed the most improvement in OS with NAC compared with surgery alone. The main limitations of our study are its retrospective design and comparison across datasets. Conclusions: Molecular subtyping may have an impact on patient benefit to NAC. If validated in additional studies, our results suggest that patients with basal tumors should be prioritized for NAC. We discovered the first single-sample classifier to subtype MIBC, which may be suitable for integration into routine clinical practice. Patient summary: Different molecular subtypes can be identified in muscle-invasive bladder cancer. Although cisplatin-based neoadjuvant chemotherapy improves patient outcomes, we identified that the benefit is highest in patients with basal tumors. Our newly discovered classifier can identify these molecular subtypes in a single patient and could be integrated into routine clinical practice after further validation. Molecular subtypes in muscle-invasive bladder cancer appear have an impact on patient response to neoadjuvant chemotherapy (NAC); namely, patients with basal tumors showed the most benefit from NAC and should be prioritized for NAC. Moreover, these subtypes can be identified in a single sample by our discovered classifier.
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13.
  • Thorn, D. B., et al. (author)
  • Polarization and anisotropic emission of K-shell radiation from heavy few electron ions
  • 2011
  • In: Canadian journal of physics (Print). - 0008-4204 .- 1208-6045. ; 89:5, s. 513-519
  • Journal article (peer-reviewed)abstract
    • The population of magnetic sublevels in hydrogen-like uranium ions has been investigated in relativistic ion-atom collisions by observing the subsequent X-ray emission. Using the gas target at the experimental storage ring facility we observed the angular emission of Lyman-alpha radiation from hydrogen-like uranium ions. The alignment parameter for three different interaction energies was measured and found to agree well with theory. In addition, the use of different gas targets allowed for the electron-impact excitation process to be observed.
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14.
  • Braun, Oscar, et al. (author)
  • Enhanced active metabolite generation and platelet inhibition with prasugrel compared to clopidogrel regardless of genotype in thienopyridine metabolic pathways
  • 2013
  • In: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 110:6, s. 1223-1231
  • Journal article (peer-reviewed)abstract
    • Clopidogrel response varies according to the presence of genetic polymorphisms. The CYP2C19*2 allele has been associated with impaired response; conflicting results have been reported for CYP2C19*17, ABCB1, and PON1 genotypes. We assessed the impact of CYP2C19, PON1, and ABCB1 polymorphisms on clopidogrel and prasugrel pharmacodynamic (PD) and pharmacokinetic (PK) parameters. Aspirin-treated patients (N=194) with coronary artery disease from two independent, prospective, randomised, multi-centre studies comparing clopidogrel (75 mg) and prasugrel (10 mg) were genotyped and classified by predicted CYP2C19 metaboliser phenotype (ultra metabolisers [UM] = *17 carriers; extensive metabolisers [EM] = *1/1 homozygotes; reduced metabolisers [RM] = *2 carriers). ABCB1 T/T and C/T polymorphisms and PON1 A/A, A/G and G/G polymorphisms were also genotyped. PD parameters were assessed using VerifyNow (R) P2Y12 and vasodilator stimulated phosphoprotein (VASP) expressed as platelet reactivity index (PR!) after 14 days of maintenance dosing. Clopi-, dogrel and prasugrel active metabolite (AM) exposure was calculated in a cohort of 96 patients. For clopidogrel, genetic variants in CYP2C19, but notABCB1 or PON1, affected PK and PD. For prasugrel, none of the measured genetic variants affected PK or PD. Compared with clopidogrel, platelet inhibition with prasugrel was greater even in the CYP2C19 UM phenotype. Prasugrel generated more AM and achieved greater platelet inhibition than clopidogrel irrespective of CYP2C19, ABCB1, and PON1 polymorphisms. The lack of effect from genetic variants on prasugrel AM generation or antiplatelet activity is consistent with previous studies in healthy volunteers and is consistent with improved efficacy in acute coronary syndrome patients managed with percutaneous coronary intervention.
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15.
  • Castro-Carrizo, A., et al. (author)
  • Mapping the 12CO J = 1-0 and J = 2-1 emission in AGB and early post-AGB circumstellar envelopes. I. The COSAS program, first sample
  • 2010
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 523:4, s. A59-
  • Journal article (peer-reviewed)abstract
    • We present COSAS (CO Survey of late AGB Stars), a project to map and analyze the 12CO J = 1−0 and J = 2−1 line emission in a representative sample of circumstellar envelopes around AGB and post-AGB stars. The survey was undertaken with the aim of investigating small- and large-scale morphological and kinematical properties of the molecular environment surrounding stars in the late AGB and early post-AGB phases. For this, COSAS combines the high sensitivity and spatial resolving power of the IRAM Plateau de Bure interferometer with the better capability of the IRAM 30 m telescope to map extended emission. The global sample encompasses 45 stars selected to span a range in chemical type, variability type, evolutionary state, and initial mass. COSAS provides means to quantify variations in the mass-loss rates, assess morphological and kinematical features, and to investigate the appearance of fast aspherical winds in the early post-AGB phase. This paper, which is the first of a series of COSAS papers, presents the results from the analyses of a first sample of 16 selected sources. The envelopes around late AGB stars are found to be mostly spherical, often mingled with features such as concentric arcs (R Cas and TX Cam), a broken spiral density pattern (TX Cam), molecular patches testifying to aspherical mass-loss (WX Psc, IK Tau, V Cyg, and S Cep), and also with well-defined axisymmetric morphologies and kinematical patterns (X Her and RX Boo). The sources span a wide range of angular sizes, from relatively compact (CRL 2362, OH 104.9+2.4 and CRL 2477) to very large (χ Cyg and TX Cam) envelopes, sometimes partially obscured by self-absorption features, which particularly for IK Tau and χ Cyg testifies to the emergence of aspherical winds in the innermost circumstellar regions. Strong axial structures with more or less complex morphologies are detected in four early post-AGB stars (IRAS 20028+3910, IRAS 23321+6545, IRAS 19475+3119 and IRAS 21282+5050) of the sub-sample.
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16.
  • Dupuy, T. J., et al. (author)
  • Multiplicity of cool dwarfs
  • 2013
  • In: Astronomical Notes - Astronomische Nachrichten. - : Wiley. - 0004-6337 .- 1521-3994. ; 334:1-2, s. 36-39
  • Journal article (peer-reviewed)abstract
    • Multiple systems have long been used to probe the origin and evolution of stars of all masses. Only in the past 10-15 years have such studies been extended to brown dwarfs and the lowest mass stars through binary surveys of both young star forming regions and the older field population. In addition, a groundswell of interest in M dwarfs in recent years has resulted in large, modern datasets for these most common stars in the Galaxy, thereby enabling renewed perspectives on their multiplicity properties. These latest observational results have in turn fueled the many theories competing to explain the formation of low-mass stars and brown dwarfs. This Cool Stars 17 splinter session examined the current state of this field by reviewing results from the numerous observational techniques - radial velocities, astrometry, direct imaging, and synoptic surveys - that have been used to study multiplicity from the earliest embedded protostars to objects in young star forming regions, old and intermediate-age clusters, as well as the more heterogeneous field population.
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17.
  • Erlinge, David, et al. (author)
  • Prasugrel 5-mg in the very elderly attenuates platelet inhibition but maintains non-inferiority to prasugrel 10-mg in non-elderly patients: The GENERATIONS trial, a pharmacodynamic and pharmacokinetic study in stable coronary artery disease patients.
  • 2013
  • In: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097. ; 62:7, s. 577-583
  • Journal article (peer-reviewed)abstract
    • OBJECTIVES: We assessed pharmacodynamic (PD) response for the reduced prasugrel 5-mg maintenance dose in very elderly (≥75y; VE) patients. BACKGROUND: In TRITON-TIMI 38, prasugrel 10-mg reduced ischemic events versus clopidogrel 75-mg, but increased bleeding in VE patients. METHODS: We examined PD and active-metabolite pharmacokinetics with prasugrel 5-mg and 10-mg and clopidogrel 75-mg in a three-period (12 days each), blinded, cross-over study in VE (n=73, mean 79±3y) or non-elderly (≥45-<65y, NE) (n=82, 56±5y) stable coronary artery disease (CAD) patients on background aspirin. Assays included light transmission aggregometry (LTA), VerifyNow(®) P2Y12 (VN-P2Y12), and VASP. The primary comparison was non-inferiority of maximum platelet aggregation (MPA) comparing the median for prasugrel 5-mg in VE versus the 75th percentile for prasugrel 10-mg in NE, using a prespecified one-sided 97.5% confidence interval for the difference <15%. RESULTS: Prasugrel 5-mg in VE met the primary pharmacodynamic non-inferiority criterion versus prasugrel 10-mg in NE. For prasugrel 5-mg, MPA was significantly lower (mean±SD, 57±14%) than clopidogrel (63±14%) (p<0.001) in VE, but higher than prasugrel 10-mg in NE (46±12%) (p<0.001). PD response by LTA, VN-P2Y12, and VASP during all treatments appeared similar between age cohorts. Prasugrel 5-mg resulted in fewer VE poor responders versus clopidogrel. Rates of mild bleeding were higher with prasugrel 10-mg, but similar for prasugrel 5-mg versus clopidogrel 75-mg. CONCLUSIONS: In aspirin-treated stable CAD patients, prasugrel 5-mg in VE attenuated platelet inhibition while meeting prespecified non-inferiority criterion versus prasugrel 10-mg in NE, with significantly better PD response and fewer poor responders compared to clopidogrel 75-mg in VE.
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18.
  • Erlinge, David, et al. (author)
  • Prasugrel 5 mg in the Very Elderly Attenuates Platelet Inhibition But Maintains Noninferiority to Prasugrel 10 mg in Nonelderly Patients
  • 2013
  • In: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 62:7, s. 577-583
  • Journal article (peer-reviewed)abstract
    • Objectives This study assessed pharmacodynamic (PD) response to the reduced prasugrel maintenance dose of 5 mg in very elderly (VE) patients (andgt;= 75 years of age). less thanbrgreater than less thanbrgreater thanBackground In the TRITON-TIMI 38 (TRial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet InhibitioN with Prasugrel-Thrombolysis In Myocardial Infarction 38) study prasugrel 10 mg reduced ischemic events versus clopidogrel 75 mg, but increased bleeding in VE patients. less thanbrgreater than less thanbrgreater thanMethods We examined PD and active metabolite pharmacokinetics (PKs) with prasugrel 5 and 10 mg and clopidogrel 75 mg in a 3-period (12 days each) blinded, crossover study in VE (n = 73; mean: 79 +/- 3 years of age) or (n 82) nonelderly (NE) (andgt;= 45 to andlt;65 years of age; mean: 56 +/- 5 years of age) stable coronary artery disease (CAD) patients receiving background aspirin. Assays included light transmission aggregometry (LTA), VerifyNow P2Y12 (VN-P2Y12), and vasodilator-associated stimulated phosphoprotein (VASP). The primary comparison was noninferiority of maximum platelet aggregation (MPA) comparing the median for prasugrel 5 mg in VE versus the 75th percentile for prasugrel 10 mg in NE, using a pre-specified 1-sided 97.5% confidence interval for the difference andlt;15%. less thanbrgreater than less thanbrgreater thanResults Prasugrel 5 mg in VE met the primary PD noninferiority criterion versus prasugrel 10 mg in NE. For prasugrel 5 mg, MPA was significantly lower (57 +/- 14%) than clopidogrel (63 +/- 14%; p andlt; 0.001) in VE but higher than prasugrel 10 mg in NE (46 +/- 12%; p andlt; 0.001). PD response by LTA, VN-P2Y12, and VASP during all treatments appeared similar between age cohorts. Prasugrel 5 mg resulted in fewer VE poor responders than clopidogrel. Rates of mild bleeding were higher with prasugrel 10 mg but similar for prasugrel 5 mg versus clopidogrel 75 mg. less thanbrgreater than less thanbrgreater thanConclusions In aspirin-treated stable CAD patients, prasugrel 5 mg in VE attenuated platelet inhibition while meeting pre-specified noninferiority criterion versus prasugrel 10 mg in NE, with significantly better PD response and fewer poor responders compared to clopidogrel 75 mg in VE. (Comparison of Prasugrel and Clopidogrel in Very Elderly and Non-Elderly Patients With Stable Coronary Artery Disease [GENERATIONS]; NCT01107912)
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19.
  • Gassner, Gregor J, et al. (author)
  • The BR1 scheme is stable for the compressible Navier–Stokes equations
  • 2018
  • In: Journal of Scientific Computing. - : Springer. - 0885-7474 .- 1573-7691. ; 77:1, s. 154-200
  • Journal article (peer-reviewed)abstract
    • We show how to modify the original Bassi and Rebay scheme (BR1) [F. Bassi and S. Rebay, A High Order Accurate Discontinuous Finite Element Method for the Numerical Solution of the Compressible Navier-Stokes Equations, Journal of Computational Physics, 131:267–279, 1997] to get a provably stable discontinuous Galerkin collocation spectral element method (DGSEM) with Gauss-Lobatto (GL) nodes for the compressible Navier-Stokes equations (NSE) on three dimensional curvilinear meshes.Specifically, we show that the BR1 scheme can be provably stable if the metric identities are discretely satisfied, a two-point average for the metric terms is used for the contravariant fluxes in the volume, an entropy conserving split form is used for the advective volume integrals, the auxiliary gradients for the viscous terms are computed from gradients of entropy variables, and the BR1 scheme is used for the interface fluxes.Our analysis shows that even with three dimensional curvilinear grids, the BR1 fluxes do not add artificial dissipation at the interior element faces. Thus, the BR1 interface fluxes preserve the stability of the discretization of the advection terms and we get either energy stability or entropy-stability for the linear or nonlinear compressible NSE, respectively.
  •  
20.
  • Gisela, Lilja, et al. (author)
  • Return to Work and Participation in Society After Out-of-Hospital Cardiac Arrest
  • 2018
  • In: Circulation-Cardiovascular Quality and Outcomes. - : Ovid Technologies (Wolters Kluwer Health). - 1941-7705 .- 1941-7713. ; 11:1
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: The aim of this study was to describe out-of-hospital cardiac arrest (OHCA) survivors' ability to participate in activities of everyday life and society, including return to work. The specific aim was to evaluate potential effects of cognitive impairment. METHODS AND RESULTS: Two hundred eighty-seven OHCA survivors included in the TTM trial (Target Temperature Management) and 119 matched control patients with ST-segment-elevation myocardial infarction participated in a follow-up 180 days post-event that included assessments of participation, return to work, emotional problems, and cognitive impairment. On the Mayo-Portland Adaptability Inventory-4 Participation Index, OHCA survivors (n=270) reported more restricted participation In everyday life and in society (47% versus 30%; P<0.001) compared with ST-segment-elevation myocardial infarction controls (n=118). Furthermore, 27% (n=36) of pre-event working OHCA survivors (n=135) compared with 7% (n=3) of pre-event working ST-segment-elevation myocardial infarction controls (n=45) were on sick leave (odds ratio, 4.9; 95% confidence interval, 1.4-16.8; P=0.01). Among the OHCA survivors assumed to return to work (n=135), those with cognitive impairment (n=55) were 3x more likely (odds ratio, 3.3; 95% confidence interval, 1.2-9.3; P=0.02) to be on sick leave compared with those without cognitive impairment (n=40; 36%, n=20, versus 15%, n=6). For OHCA survivors, the variables that were found most predictive for a lower participation were depression, restricted mobility, memory impairment, novel problem-solving difficulties, fatigue, and slower processing speed. CONCLUSIONS: OHCA survivors reported a more restricted societal participation 6 months post-arrest, and their return to work was lower compared with ST-segment-elevation myocardial infarction controls. Cognitive impairment was significantly associated with lower participation, together with the closely related symptoms of fatigue, depression, and restricted mobility. These predictive variables may be used during follow-up to identify OHCA survivors at risk of a less successful recovery that may benefit from further support and rehabilitation.
  •  
21.
  • Gumberidze, Alexandre, et al. (author)
  • Angular Distribution of Characteristic Radiation Following the Excitation of He-Like Uranium in Relativistic Collisions
  • 2021
  • In: Atoms. - : MDPI AG. - 2218-2004. ; 9:2
  • Journal article (peer-reviewed)abstract
    • In this paper, we present an experimental and theoretical study of excitation processes for the heaviest stable helium-like ion, that is, He-like uranium occurring in relativistic collisions with hydrogen and argon targets. In particular, we concentrate on angular distributions of the characteristic K alpha radiation following the K -> L excitation of He-like uranium. We pay special attention to the magnetic sub-level population of the excited 1s2l(j) states, which is directly related to the angular distribution of the characteristic K alpha radiation. We show that the experimental data can be well described by calculations taking into account the excitation by the target nucleus as well as by the target electrons. Moreover, we demonstrate for the first time an important influence of the electron-impact excitation process on the angular distributions of the K alpha radiation produced by excitation of He-like uranium in collisions with different targets.
  •  
22.
  • Gumberidze, A., et al. (author)
  • Electron- and proton-impact excitation of heliumlike uranium in relativistic collisions
  • 2019
  • In: Physical Review A: covering atomic, molecular, and optical physics and quantum information. - 2469-9926 .- 2469-9934. ; 99:3
  • Journal article (peer-reviewed)abstract
    • We have studied the K-shell excitation of He-like uranium (U90+) in relativistic collisions with hydrogen and argon atoms. Performing measurements with different targets, as well as with different collision energies, enabled us to explore the proton- (nucleus-) impact excitation as well as the electron-impact excitation process for the heaviest He-like ion. The large fine-structure splitting in uranium allowed us to partially resolve excitation into different L-shell levels. State-of-the-art relativistic calculations which include excitation mechanisms due to the interaction with both protons (nucleus) and electrons are in good agreement with the experimental findings. Moreover, our experimental data clearly demonstrate the importance of including the generalized Breit interaction in the treatment of the electron-impact excitation process.
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23.
  • Gurbel, Paul A., et al. (author)
  • The effect of CYP2C19 gene polymorphisms on the pharmacokinetics and pharmacodynamics of prasugrel 5-mg, prasugrel 10-mg and clopidogrel 75-mg in patients with coronary artery disease
  • 2014
  • In: Thrombosis and Haemostasis. - : Schattauer. - 0340-6245 .- 2567-689X. ; 112:3, s. 589-597
  • Journal article (peer-reviewed)abstract
    • CYP2C19 genotype has been shown to impact response to clopidogrel 75-mg but not prasugrel 10-mg. Here, we assessed effects of CYP2C19 metaboliser status on pharmacokinetics (PK) and pharmacodynamic (PD) responses to prasugrel 5-mg and 10-mg and clopidogrel 75-mg using data from two PK/PD studies in stable coronary artery disease (CAD) patients (GENERATIONS and FEATHER). Active metabolite concentrations (area under the curve, AUC([0-tlast])), maximum platelet aggregation (MPA) measured by light transmission aggregometry, vasodilator-stimulated phosphoprotein platelet reactivity index, and VerifyNow P2Y12-platelet reaction units (VN-PRU) were analysed by CYP2C19-predicted phenotype (extensive metaboliser [EM; N=154], *2-*8 non-carriers, vs reduced metaboliser [RM; N=41],*2-*8 carriers/*17 non-carriers). AUC((0-tlast)) was unaffected by metaboliser status for prasugrel 5-mg and 10-mg (geometric mean EM/RM ratios 1.00, 95% confidence interval [Cl]: 0.86,1.17, p>0.99; and 0.97, 95% CI:0.85,1.12, p=0.71, respectively), but was lower among RMs receiving clopidogrel 75-mg (1.37, 95% CI:1.14,1.65, p<0.001). Platelet reactivity was not significantly affected by CYP2C19 metaboliser status for prasugrel 5-mg, or for prasugrel 10-mg by MPA and VN-PRU, but for clopidogrel 75-mg was significantly higher in reduced metabolisers (all measures p<0.01). Prasugrel 10-mg showed greater antiplatelet effects vs clopidogrel 75-mg (all comparisons p<0.001). Prasugrel 5-mg showed greater antiplatelet effects vs clopidogrel 75-mg in RMs (all p<0.001), and comparable effects in EMs (all p >= 0.37). In contrast to clopidogrel, prasugrel active metabolite PK was not influenced by CYP2C19 genotype. Antiplatelet effect for prasugrel 10-mg was greater irrespective of metaboliser status and for prasugrel 5-mg was greater for RMs and comparable for EMs as compared to clopidogrel 75-mg.
  •  
24.
  • Jakubowski, Joseph A., et al. (author)
  • The influence of body size on the pharmacodynamic and pharmacokinetic response to clopidogrel and prasugrel : A retrospective analysis of the FEATHER study
  • 2014
  • In: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 134:3, s. 552-557
  • Journal article (peer-reviewed)abstract
    • Introduction: Patients treated with clopidogrel who have higher body size exhibit greater platelet reactivity than patients with lower body size. In a retrospective analysis of the FEATHER trial, we examined the relationship between platelet response to thienopyridines clopidogrel 75 mg (Clop-75), prasugrel 5 mg (Pras-5), and prasugrel 10 mg (Pras-10) using 3 body size indices: body weight (BW), body mass index (BMI), and body surface area (BSA). Relationships were assessed as continuous variables and as 4 incremental body size groups. Materials and Methods: Aspirin-treated patients with stable coronary artery disease (N = 72) and a BW range of 45-134 kg received Clop-75, Pras-5, and Pras-10 in a 3-period, blinded, cross-over study. Platelet assays included maximum platelet aggregation (MPA) to 20 mu M ADP by light transmission aggregometry, VerifyNow-P2Y12 reaction units (PRU), and vasodilator-associated stimulated phosphoprotein (VASP) phosphorylation platelet reactivity index (PRI). Exposure to active metabolites (AMs) was also assessed. Results: Body size was a determinant of AM exposure and residual platelet reactivity regardless of type and dose of thienopyridine. BW and BSA demonstrated marginally stronger correlations with platelet reactivity; VASP-PRI demonstrated a stronger correlation with the body size than the other tests. Correlation coefficients ranged from a high of 0.64 (BW vs. PRI on Pras-5) to a low of 0.34 (BMI vs. MPA on Pras-10), but all were statistically significant (p < 0.01). Conclusions: Using a comprehensive selection of body size indices, AM exposures, platelet function tests, and thienopyridine doses, we demonstrated a consistent inverse relationship between body size and response to clopidogrel and prasugrel. (C) 2014 Elsevier Ltd. All rights reserved.
  •  
25.
  • Jakubowski, Joseph A., et al. (author)
  • The Rationale for and Clinical Pharmacology of Prasugrel 5 mg
  • 2017
  • In: American Journal of Cardiovascular Drugs. - : Springer Science and Business Media LLC. - 1175-3277 .- 1179-187X. ; 17:2, s. 109-121
  • Journal article (peer-reviewed)abstract
    • Prasugrel is a third-generation thienopyridine platelet P2Y12 adenosine diphosphate (ADP) receptor antagonist administered with aspirin for the treatment of patients with acute coronary syndrome (ACS) with planned percutaneous coronary intervention. Prasugrel is administered periprocedurally at an oral loading dose of 60 mg followed by daily maintenance doses (MDs) of 10 mg for most patients and 5 mg for patients weighing <60 kg or aged ≥75 years. Data from a prasugrel phase III study, TRITON-TIMI 38, suggested that a lower MD might be more suitable for patients weighing <60 kg or aged ≥75 years; subsequent pharmacokinetic and pharmacodynamic studies have indicated that prasugrel 5 mg reduced platelet reactivity in these populations to an extent similar to that of prasugrel 10 mg in heavier or younger patients. Clinical experience with prasugrel 5 mg is limited, and additional studies are needed to verify the clinical efficacy and safety of this dose in these challenging populations.
  •  
26.
  •  
27.
  • Ng, Janice S.W., et al. (author)
  • Using Tetracysteine-Tagged TDP-43 with a Biarsenical Dye to Monitor Real-Time Trafficking in a Cell Model of Amyotrophic Lateral Sclerosis
  • 2019
  • In: Biochemistry. - : American Chemical Society (ACS). - 1520-4995 .- 0006-2960. ; 58:39, s. 4086-4095
  • Journal article (peer-reviewed)abstract
    • TAR DNA-binding protein 43 (TDP-43) has been identified as the major constituent of the proteinaceous inclusions that are characteristic of most forms of amyotrophic lateral sclerosis (ALS) and ubiquitin positive frontotemporal lobar degeneration (FTLD). Wild type TDP-43 inclusions are a pathological hallmark of >95% of patients with sporadic ALS and of the majority of familial ALS cases, and they are also found in a significant proportion of FTLD cases. ALS is the most common form of motor neuron disease, characterized by progressive weakness and muscular wasting, and typically leads to death within a few years of diagnosis. To determine how the translocation and misfolding of TDP-43 contribute to ALS pathogenicity, it is crucial to define the dynamic behavior of this protein within the cellular environment. It is therefore necessary to develop cell models that allow the location of the protein to be defined. We report the use of TDP-43 with a tetracysteine tag for visualization using fluorogenic biarsenical compounds and show that this model displays features of ALS observed in other cell models. We also demonstrate that this labeling procedure enables live-cell imaging of the translocation of the protein from the nucleus into the cytosol.
  •  
28.
  • Wagner, Henrik, et al. (author)
  • Higher body weight patients on clopidogrel maintenance therapy have lower active metabolite concentrations, lower levels of platelet inhibition, and higher rates of poor responders than low body weight patients
  • 2014
  • In: Journal of Thrombosis and Thrombolysis. - : Springer Science and Business Media LLC. - 0929-5305 .- 1573-742X. ; 38:2, s. 127-136
  • Journal article (peer-reviewed)abstract
    • Body weight is a predictor of clopidogrel response. However, no prospective studies have compared pharmacodynamic (PD) and pharmacokinetic (PK) data based on body weight. We compared PD and PK effects of clopidogrel 75 mg in low body weight (LBW, <60 kg) and higher body weight (HBW, >= 60 kg) patients with stable coronary artery disease. LBW (n = 34, 56.4 +/- 3.7 kg) and HBW (n = 38, 84.7 +/- 14.9 kg) aspirin-treated patients received clopidogrel 75 mg for 10-14 days. The area under the concentration-time curve of active metabolite (Clop-AM) calculated through the last quantifiable concentration up to 4 h postdose, AUC((0-tlast)), was calculated by non-compartmental methods. Light transmission aggregometry (LTA) (maximum platelet aggregation and inhibition of platelet aggregation to 20 mu M adenosine diphosphate (ADP), and residual platelet aggregation to 5 mu M ADP), VerifyNow (R) P2Y12 reaction units (PRU), and vasodilator-associated stimulated phosphoprotein phosphorylation platelet reactivity index (VASP-PRI) were performed. Mean AUC((0-tlast)) was lower in HBW than LBW patients: 12.8 versus 17.9 ng h/mL. HBW patients had higher platelet reactivity as measured by LTA (all p <= 0.01), PRU (207 +/- 68 vs. 152 +/- 57, p < 0.001), and VASP-PRI (56 +/- 18 vs. 39 +/- 17, p < 0.001). More HBW patients exhibited high on-treatment platelet reactivity (HPR) using PRU (35 vs. 9 %) and VASP-PRI (65 vs. 27 %). Body weight correlated with PRU and VASP-PRI (both p < 0.001), and inversely with log transformed AUC((0-tlast)) (p < 0.001). In conclusion, HBW patients had lower levels of Clop-AM, and higher platelet reactivity and rates of HPR than LBW subjects, contributing to their suboptimal response to clopidogrel.
  •  
29.
  • Western, Benedikte, et al. (author)
  • Dropout from exercise trials among cancer survivors—An individual patient data meta-analysis from the POLARIS study
  • 2024
  • In: Scandinavian Journal of Medicine and Science in Sports. - Chichester, West Sussex : Wiley-Blackwell Publishing Inc.. - 0905-7188 .- 1600-0838. ; 34:2, s. 1-10
  • Journal article (peer-reviewed)abstract
    • Introduction: The number of randomized controlled trials (RCTs) investigating the effects of exercise among cancer survivors has increased in recent years; however, participants dropping out of the trials are rarely described. The objective of the present study was to assess which combinations of participant and exercise program characteristics were associated with dropout from the exercise arms of RCTs among cancer survivors. Methods: This study used data collected in the Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS) study, an international database of RCTs investigating the effects of exercise among cancer survivors. Thirty-four exercise trials, with a total of 2467 patients without metastatic disease randomized to an exercise arm were included. Harmonized studies included a pre and a posttest, and participants were classified as dropouts when missing all assessments at the post-intervention test. Subgroups were identified with a conditional inference tree. Results: Overall, 9.6% of the participants dropped out. Five subgroups were identified in the conditional inference tree based on four significant associations with dropout. Most dropout was observed for participants with BMI >28.4 kg/m2, performing supervised resistance or unsupervised mixed exercise (19.8% dropout) or had low-medium education and performed aerobic or supervised mixed exercise (13.5%). The lowest dropout was found for participants with BMI >28.4 kg/m2 and high education performing aerobic or supervised mixed exercise (5.1%), and participants with BMI ≤28.4 kg/m2 exercising during (5.2%) or post (9.5%) treatment. Conclusions: There are several systematic differences between cancer survivors completing and dropping out from exercise trials, possibly affecting the external validity of exercise effects. © 2024 The Authors. Scandinavian Journal of Medicine & Science In Sports published by John Wiley & Sons Ltd.
  •  
30.
  • Winters, Andrew Ross, et al. (author)
  • A comparative study on polynomial dealiasing and split form discontinuous Galerkin schemes for under-resolved turbulence computations
  • 2018
  • In: Journal of Computational Physics. - : Elsevier. - 0021-9991 .- 1090-2716. ; 372, s. 1-21
  • Journal article (peer-reviewed)abstract
    • This work focuses on the accuracy and stability of high-order nodal discontinuous Galerkin (DG) methods for under-resolved turbulence computations. In particular we consider the inviscid Taylor-Green vortex (TGV) flow to analyse the implicit large eddy simulation (iLES) capabilities of DG methods at very high Reynolds numbers. The governing equations are discretised in two ways in order to suppress aliasing errors introduced into the discrete variational forms due to the under-integration of non-linear terms. The first, more straightforward way relies on consistent/over-integration, where quadrature accuracy is improved by using a larger number of integration points, consistent with the degree of the non-linearities. The second strategy, originally applied in the high-order finite difference community, relies on a split (or skew-symmetric) form of the governing equations. Different split forms are available depending on how the variables in the non-linear terms are grouped. The desired split form is then built by averaging conservative and non-conservative forms of the governing equations, although conservativity of the DG scheme is fully preserved. A preliminary analysis based on Burgers’ turbulence in one spatial dimension is conducted and shows the potential of split forms in keeping the energy of higher-order polynomial modes close to the expected levels. This indicates that the favourable dealiasing properties observed from split-form approaches in more classical schemes seem to hold for DG. The remainder of the study considers a comprehensive set of (under-resolved) computations of the inviscid TGV flow and compares the accuracy and robustness of consistent/over-integration and split form discretisations based on the local Lax-Friedrichs and Roe-type Riemann solvers. Recent works showed that relevant split forms can stabilize higher-order inviscid TGV test cases otherwise unstable even with consistent integration. Here we show that stable high-order cases achievable with both strategies have comparable accuracy, further supporting the good dealiasing properties of split form DG. The higher-order cases achieved only with split form schemes also displayed all the main features expected from consistent/over-integration. Among test cases with the same number of degrees of freedom, best solution quality is obtained with Roe-type fluxes at moderately high orders (around sixth order). Solutions obtained with very high polynomial orders displayed spurious features attributed to a sharper dissipation in wavenumber space. Accuracy differences between the two dealiasing strategies considered were, however, observed for the low-order cases, which also yielded reduced solution quality compared to high-order results.
  •  
31.
  • Winters, Mikael, 1976, et al. (author)
  • Control of electron transfer in a conjugated porphyrin dimer by selective excitation of planar and perpendicular conformers
  • 2007
  • In: Chemistry - A European Journal. - : Wiley. - 1521-3765 .- 0947-6539. ; 13:26, s. 7385-7394
  • Journal article (peer-reviewed)abstract
    • A donor-acceptor system is presented in which the electron-transfer rates can be sensitively controlled by means of excitation wavelength and temperature. The electron donor is a butadiyne-linked zinc porphyrin dimer that is connected to a C-60 electron acceptor. The broad distribution of conformations allowed by the butadiyne linker makes it possible to selectively excite perpendicular or planar donor conformers and thereby prepare separate initial states with driving forces for electron transfer that differ by almost 0.2 eV This, as well as significant differences in electronic coupling, leads to distinctly different rate constants for electron transfer, which in consequence can be controlled by changing excitation wavelength. By extending the system with a secondary donor (ferrocene), a second, long-range charge-separated state can be formed. This system has been used to test the influence of conformational heterogeneity on electron transfer mediated by the porphyrin dimer in the ground state. It was found that if the dimer is forced to a planar conformation by means of a bidentate ligand, the charge recombination rate increased by an order of magnitude relative to the unconstrained system. This illustrates how control of conformation of a molecular wire can affect its behaviour.
  •  
32.
  • Winters, Mikael, 1976, et al. (author)
  • Probing the efficiency of electron transfer through porphyrin-based molecular wires
  • 2007
  • In: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 1520-5126 .- 0002-7863. ; 129:14, s. 4291-4297
  • Journal article (peer-reviewed)abstract
    • Electron transfer over long distances is important for many future applications in molecular electronics and solar energy harvesting. In these contexts, it is of great interest to find molecular systems that are able to efficiently mediate electrons in a controlled manner over nanometer distances, that is, structures that function as molecular wires. Here we investigate a series of butadiyne-linked porphyrin oligomers with ferrocene and fullerene (C-60) terminals separated by one, two, or four porphyrin units (P-n, n = 1, 2, or 4). When the porphyrin oligomer bridges are photoexcited, long-range charge separated states are formed through a series of electron-transfer steps and the rates of photoinduced charge separation and charge recombination in these systems were elucidated using time-resolved absorption and emission measurements. The rates of long-range charge recombination, through these conjugated porphyrin oligomers, are remarkably fast (k(CR2) = 15 - 1.3 x 10(8) s(-1)) and exhibit very weak distance dependence, particularly comparing the systems with n = 2 and n = 4. The observation that the porphyrin tetramer mediates fast long-range charge transfer, over 65 angstrom, is significant for the application of these structures as molecular wires.
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33.
  • Aalto, Susanne, 1964, et al. (author)
  • Detection of HCN, HCO+, and HNC in the Mrk 231 molecular outflow. Dense molecular gas in the AGN wind
  • 2012
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 537, s. 44-51
  • Journal article (peer-reviewed)abstract
    • We obtained high-resolution (1.''55 × 1.''28) observations of HCN, HCO+, HNC 1-0 and HC3N 10-9 of the ultraluminous galaxy (ULIRG) Mrk 231 with the IRAM Plateau de Bure Interferometer.Results: We detect luminous emission from HCN, HCO+ and HNC 1-0 in the QSO ULIRG Mrk 231. All three lines show broad line wings - which are particularly prominent for HCN. Velocities are found to be similar ( ≈ ± 750 km s-1) to those found for CO 1-0. This is the first time bright HCN, HCO+ and HNC emission has been detected in a large-scale galactic outflow. We find that both the blue- and red-shifted line wings are spatially extended by at least 0.''75 (>700 pc) in a north-south direction. The line wings are brighter (relative to the line center intensity) in HCN than in CO 1-0 and line ratios suggest that the molecular outflow consists of dense (n > 104 cm-3) and clumpy gas with a high HCN abundance X(HCN) > 10-8. These properties are consistent with the molecular gas being compressed and fragmented by shocks in the outflow. Alternatively, HCN is instead pumped by mid-IR continuum, but we propose that this effect is not strong for the spatially extended outflowing gas. In addition, we find that the rotation of the main disk, in east-west direction, is also evident in the HCN, HCO+ and HNC line emission. An unexpectedly bright HC3N 10-9 line is detected inside the central 400 pc of Mrk 231. This HC3N emission may emerge from a shielded, dust-enshrouded region within the inner 40-50 pc where the gas is heated to high temperatures (200-300 K) by the AGN.
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34.
  • Aalto, Susanne, 1964, et al. (author)
  • High resolution observations of HCN and HCO+J = 3–2 in the disk and outflow of Mrk 231 -- Detection of vibrationally excited HCN in the warped nucleus
  • 2015
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 574, s. 85-
  • Journal article (peer-reviewed)abstract
    • Aims. Our goal is to study molecular gas properties in nuclei and large scale outflows/winds from active galactic nuclei (AGNs) and starburst galaxies.Methods. We obtained high resolution (0.̋25 to 0.̋90) observations of HCN and HCO+J = 3 → 2 of the ultraluminous QSO galaxy Mrk 231 with the IRAM Plateau de Bure Interferometer (PdBI).Results. We find luminous HCN and HCO+J = 3 → 2 emission in the main disk and we detect compact (r ≲ 0''̣1 (90 pc)) vibrationally excited HCN J = 3 → 2ν2 = 1f emission centred on the nucleus. The velocity field of the vibrationally excited HCN is strongly inclined (position angle PA = 155°) compared to the east-west rotation of the main disk. The nuclear (r ≲ 0.̋1) molecular mass is estimated to 8 × 108 M⊙ with an average N(H2) of 1.2 × 1024 cm-2. Prominent, spatially extended (≳350 pc) line wings are found for HCN J = 3 → 2 with velocities up to ± 750 km s-1. Line ratios indicate that the emission is emerging in dense gas n = 104−5 × 105 cm-3 of elevated HCN abundance X(HCN) = 10-8−10-6. The highest X(HCN) also allows for the emission to originate in gas of more moderate density. We tentatively detect nuclear emission from the reactive ion HOC+ with HCO+/HOC+ = 10−20.Conclusions. The HCN ν2 = 1f line emission is consistent with the notion of a hot, dusty, warped inner disk of Mrk 231 where the ν2 = 1f line is excited by bright mid-IR 14 μm continuum. We estimate the vibrational temperature Tvib to 200−400 K. Based on relative source sizes we propose that 50% of the main HCN emission may have its excitation affected by the radiation field through IR pumping of the vibrational ground state. The HCN emission in the line wings, however, is more extended and thus likely not strongly affected by IR pumping. Our results reveal that dense clouds survive (and/or are formed) in the AGN outflow on scales of at least several hundred pc before evaporating or collapsing. The elevated HCN abundance in the outflow is consistent with warm chemistry possibly related to shocks and/or X-ray irradiated gas. An upper limit to the mass and momentum flux is 4 × 108 M⊙ and 12LAGN/c, respectively, and we discuss possible driving mechanisms for the dense outflow.
  •  
35.
  • Alfredsson, Joakim, et al. (author)
  • Predicting the risk of bleeding during dual antiplatelet therapy after acute coronary syndromes
  • 2017
  • In: Heart. - : BMJ PUBLISHING GROUP. - 1355-6037 .- 1468-201X. ; 103:15, s. 1168-1176
  • Journal article (peer-reviewed)abstract
    • Objectives Dual antiplatelet therapy (DAPT) with aspirin + a P2Y12 inhibitor is recommended for at least 12 months for patients with acute coronary syndrome (ACS), with shorter durations considered for patients with increased bleeding risk. However, there are no decision support tools available to predict an individual patients bleeding risk during DAPT treatment in the post-ACS setting. Methods To develop a longitudinal bleeding risk prediction model, we analysed 9240 patients with unstable angina/non-ST segment elevation myocardial infarction (NSTEMI) from the Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes (TRILOGY ACS) trial, who were managed without revascularisation and treated with DAPT for a median of 14.8 months. Results We identified 10 significant baseline predictors of non-coronary artery bypass grafting (CABG)-related Global Use of Strategies to Open Occluded Arteries (GUSTO) severe/life-threatening/moderate bleeding: age, sex, weight, NSTEMI (vs unstable angina), angiography performed before randomisation, prior peptic ulcer disease, creatinine, systolic blood pressure, haemoglobin and treatment with beta-blocker. The five significant baseline predictors of Thrombolysis In Myocardial Infarction (TIMI) major or minor bleeding included age, sex, angiography performed before randomisation, creatinine and haemoglobin. The models showed good predictive accuracy with Therneaus C-indices: 0.78 (SE=0.024) for the GUSTO model and 0.67 (SE=0.023) for the TIMI model. Internal validation with bootstrapping gave similar C-indices of 0.77 and 0.65, respectively. External validation demonstrated an attenuated C-index for the GUSTO model (0.69) but not the TIMI model (0.68). Conclusions Longitudinal bleeding risks during treatment with DAPT in patients with ACS can be reliably predicted using selected baseline characteristics. The TRILOGY ACS bleeding models can inform riskbenefit considerations regarding the duration of DAPT following ACS.
  •  
36.
  • Aran Terol, P., et al. (author)
  • Solvent exposure of Tyr10 as a probe of structural differences between monomeric and aggregated forms of the amyloid-β peptide
  • 2015
  • In: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 468:4, s. 696-701
  • Journal article (peer-reviewed)abstract
    • Aggregation of amyloid-β (Aβ) peptides is a characteristic pathological feature of Alzheimer's disease. We have exploited the relationship between solvent exposure and intrinsic fluorescence of a single tyrosine residue, Tyr10, in the Aβ sequence to probe structural features of the monomeric, oligomeric and fibrillar forms of the 42-residue Aβ1-42. By monitoring the quenching of Tyr10 fluorescence upon addition of water-soluble acrylamide, we show that in Aβ1-42 oligomers this residue is solvent-exposed to a similar extent to that found in the unfolded monomer. By contrast, Tyr10 is significantly shielded from acrylamide quenching in Aβ1-42 fibrils, consistent with its proximity to the fibrillar cross-β core. Furthermore, circular dichroism measurements reveal that Aβ1-42 oligomers have a considerably lower β-sheet content than the Aβ1-42 fibrils, indicative of a less ordered molecular arrangement in the former. Taken together these findings suggest significant differences in the structural assembly of oligomers and fibrils that are consistent with differences in their biological effects.
  •  
37.
  • Ardern, Clare L, et al. (author)
  • Implementing the 27 PRISMA 2020 Statement items for systematic reviews in the sport and exercise medicine, musculoskeletal rehabilitation and sports science fields : The PERSiST (implementing Prisma in Exercise, Rehabilitation, Sport medicine and SporTs science) guidance
  • 2022
  • In: British Journal of Sports Medicine. - : BMJ. - 0306-3674 .- 1473-0480. ; 56:4, s. 175-195
  • Journal article (peer-reviewed)abstract
    • Poor reporting of medical and healthcare systematic reviews is a problem from which the sports and exercise medicine, musculoskeletal rehabilitation, and sports science fields are not immune. Transparent, accurate and comprehensive systematic review reporting helps researchers replicate methods, readers understand what was done and why, and clinicians and policy-makers implement results in practice. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement and its accompanying Explanation and Elaboration document provide general reporting examples for systematic reviews of healthcare interventions. However, implementation guidance for sport and exercise medicine, musculoskeletal rehabilitation, and sports science does not exist. The Prisma in Exercise, Rehabilitation, Sport medicine and SporTs science (PERSiST) guidance attempts to address this problem. Nineteen content experts collaborated with three methods experts to identify examples of exemplary reporting in systematic reviews in sport and exercise medicine (including physical activity), musculoskeletal rehabilitation (including physiotherapy), and sports science, for each of the PRISMA 2020 Statement items. PERSiST aims to help: (1) systematic reviewers improve the transparency and reporting of systematic reviews and (2) journal editors and peer reviewers make informed decisions about systematic review reporting quality.
  •  
38.
  • Bohm, Marvin, et al. (author)
  • An entropy stable nodal discontinuous Galerkin method for the resistive MHD equations. Part I : Theory and numerical verification
  • 2018
  • In: Journal of Computational Physics. - : Elsevier. - 0021-9991 .- 1090-2716.
  • Journal article (peer-reviewed)abstract
    • The first paper of this series presents a discretely entropy stable discontinuous Galerkin (DG) method for the resistive magnetohydrodynamics (MHD) equations on three-dimensional curvilinear unstructured hexahedral meshes. Compared to other fluid dynamics systems such as the shallow water equations or the compressible Navier-Stokes equations, the resistive MHD equations need special considerations because of the divergence-free constraint on the magnetic field. For instance, it is well known that for the symmetrization of the ideal MHD system as well as the continuous entropy analysis a non-conservative term proportional to the divergence of the magnetic field, typically referred to as the Powell term, must be included. As a consequence, the mimicry of the continuous entropy analysis in the discrete sense demands a suitable DG approximation of the non-conservative terms in addition to the ideal MHD terms.This paper focuses on the resistive MHD equations: Our first contribution is a proof that the resistive terms are symmetric and positive-definite when formulated in entropy space as gradients of the entropy variables, which enables us to show that the entropy inequality holds for the resistive MHD equations. This continuous analysis is the key for our DG discretization and guides the path for the construction of an approximation that discretely mimics the entropy inequality, typically termed entropy stability. Our second contribution is a detailed derivation and analysis of the discretization on three-dimensional curvilinear meshes. The discrete analysis relies on the summation-by-parts property, which is satisfied by the DG spectral element method (DGSEM) with Legendre-Gauss-Lobatto (LGL) nodes. Although the divergence-free constraint is included in the non-conservative terms, the resulting method has no particular treatment of the magnetic field divergence errors, which might pollute the solution quality. Our final contribution is the extension of the standard resistive MHD equations and our DG approximation with a divergence cleaning mechanism that is based on a generalized Lagrange multiplier (GLM).As a conclusion to the first part of this series, we provide detailed numerical validations of our DGSEM method that underline our theoretical derivations. In addition, we show a numerical example where the entropy stable DGSEM demonstrates increased robustness compared to the standard DGSEM.
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39.
  • Bohm, Marvin, et al. (author)
  • Multi-element SIAC Filter for Shock Capturing Applied to High-Order Discontinuous Galerkin Spectral Element Methods
  • 2019
  • In: Journal of Scientific Computing. - : Springer-Verlag New York. - 0885-7474 .- 1573-7691. ; 81:2, s. 820-844
  • Journal article (peer-reviewed)abstract
    • We build a multi-element variant of the smoothness increasing accuracy conserving (SIAC) shock capturing technique proposed for single element spectral methods by Wissink et al. (J Sci Comput 77:579–596, 2018). In particular, the baseline scheme of our method is the nodal discontinuous Galerkin spectral element method (DGSEM) for approximating the solution of systems of conservation laws. It is well known that high-order methods generate spurious oscillations near discontinuities which can develop in the solution for nonlinear problems, even when the initial data is smooth. We propose a novel multi-element SIAC filtering technique applied to the DGSEM as a shock capturing method. We design the SIAC filtering such that the numerical scheme remains high-order accurate and that the shock capturing is applied adaptively throughout the domain. The shock capturing method is derived for general systems of conservation laws. We apply the novel SIAC filter to the two-dimensional Euler and ideal magnetohydrodynamics equations to several standard test problems with a variety of boundary conditions.
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40.
  • Bost, J. P., et al. (author)
  • Delivery of Oligonucleotide Therapeutics: Chemical Modifications, Lipid Nanoparticles, and Extracellular Vesicles
  • 2021
  • In: Acs Nano. - : American Chemical Society (ACS). - 1936-0851 .- 1936-086X. ; 15:9, s. 13993-14021
  • Journal article (peer-reviewed)abstract
    • Oligonucleotides (ONs) comprise a rapidly growing class of therapeutics. In recent years, the list of FDA-approved ON therapies has rapidly expanded. ONs are small (15-30 bp) nucleotide-based therapeutics which are capable of targeting DNA and RNA as well as other biomolecules. ONs can be subdivided into several classes based on their chemical modifications and on the mechanisms of their target interactions. Historically, the largest hindrance to the widespread usage of ON therapeutics has been their inability to effectively internalize into cells and escape from endosomes to reach their molecular targets in the cytosol or nucleus. While cell uptake has been improved, "endosomal escape" remains a significant problem. There are a range of approaches to overcome this, and in this review, we focus on three: altering the chemical structure of the ONs, formulating synthetic, lipid-based nanoparticles to encapsulate the ONs, or biologically loading the ONs into extracellular vesicles. This review provides a background to the design and mode of action of existing FDA-approved ONs. It presents the most common ON classifications and chemical modifications from a fundamental scientific perspective and provides a roadmap of the cellular uptake pathways by which ONs are trafficked. Finally, this review delves into each of the above-mentioned approaches to ON delivery, highlighting the scientific principles behind each and covering recent advances.
  •  
41.
  • Bost, Jeremy P., et al. (author)
  • Novel endosomolytic compounds enable highly potent delivery of antisense oligonucleotides
  • 2022
  • In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1
  • Journal article (peer-reviewed)abstract
    • The therapeutic and research potentials of oligonucleotides (ONs) have been hampered in part by their inability to effectively escape endosomal compartments to reach their cytosolic and nuclear targets. Splice-switching ONs (SSOs) can be used with endosomolytic small molecule compounds to increase functional delivery. So far, development of these compounds has been hindered by a lack of high-resolution methods that can correlate SSO trafficking with SSO activity. Here we present in-depth characterization of two novel endosomolytic compounds by using a combination of microscopic and functional assays with high spatiotemporal resolution. This system allows the visualization of SSO trafficking, evaluation of endosomal membrane rupture, and quantitates SSO functional activity on a protein level in the presence of endosomolytic compounds. We confirm that the leakage of SSO into the cytosol occurs in parallel with the physical engorgement of LAMP1-positive late endosomes and lysosomes. We conclude that the new compounds interfere with SSO trafficking to the LAMP1-positive endosomal compartments while inducing endosomal membrane rupture and concurrent ON escape into the cytosol. The efficacy of these compounds advocates their use as novel, potent, and quick-acting transfection reagents for antisense ONs.
  •  
42.
  • Braun, Oscar, et al. (author)
  • Greater reduction of platelet activation markers and platelet-monocyte aggregates by prasugrel compared to clopidogrel in stable coronary artery disease
  • 2008
  • In: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 100:4, s. 626-633
  • Journal article (peer-reviewed)abstract
    • Prasugrel, a novel P2Y(12) ADP-receptor antagonist, has been reported to achieve greater inhibition of platelet aggregation compared to clopidogrel as assessed by light transmission aggregometry. It was the objective of this study to investigate the effect of prasugrel on alternative markers of platelet activation in comparison to a high loading dose and the approved maintenance dose of clopidogrel. One hundred ten aspirin-treated patients with stable coronary artery disease were randomized to a loading dose (LD, day 1)/ maintenance dose (MD, days 2-29) of prasugrel 60 mg/10 mg or clopidogrel 600 mg/75 mg. Platelet activation markers were analyzed by whole blood flow cytometry pre-dose and at 2 and 24 hours after LD and pre-dose at 14 and 29 days. After stimulation with 20 muM ADP, 2 hours after LD, significantly lower expression of activated GPIIb/IIIa (4.3 vs. 21.8 [mean fluorescent intensity (MFI)], p < 0.001) and P-selectin (2.0 vs. 11.7 MFI, p < 0.001) along with decreased formation of platelet-monocyte aggregates (16.4% vs. 29.6% positive cells, p < 0.001) was observed with prasugrel versus clopidogrel. All these effects were maintained through 24 hours and during the MD period. In conclusion, prasugrel 60 mg LD and 10 mg MD inhibit several markers of platelet activation and the formation of platelet-monocyte aggregates more effectively than a 600 mg LD and 75 mg MD of clopidogrel. Attenuated platelet aggregation and reduced expression of platelet pro-coagulant and pro-inflammatory markers with prasugrel suggest the potential to reduce cardiovascular events both in the acute setting and in long-term treatment.
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43.
  •  
44.
  • Chan, Mark Y., et al. (author)
  • Temporal biomarker profiling reveals longitudinal changes in risk of death or myocardial infarction in Non-ST-segment elevation acute coronary syndrome
  • 2017
  • In: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 63:7, s. 1214-1226
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: There are conflicting data on whether changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity C-reactive protein (hs-CRP) concentrations between time points (delta NT-proBNP and hs-CRP) are associated with a change in prognosis. METHODS: We measured NT-proBNP and hs-CRP at 3 time points in 1665 patients with non-ST-segment elevation acute coronary syndrome (NSTEACS). Cox proportional hazards was applied to the delta between temporal measurements to determine the continuous association with cardiovascular events. Effect estimates for delta NT-proBNP and hs-CRP are presented per 40% increase as the basic unit of temporal change. RESULTS: Median NT-proBNP was 370.0 (25th, 75th percentiles, 130.0, 996.0), 340.0 (135.0, 875.0), and 267.0 (111.0, 684.0) ng/L; and median hs-CRP was 4.6 (1.7, 13.1), 1.9 (0.8, 4.5), and 1.8 (0.8, 4.4) mg/L at baseline, 30 days, and 6 months, respectively. The deltas between baseline and 6 months were the most prognostically informative. Every 40% increase of delta NTproBNP (baseline to 6 months) was associated with a 14% greater risk of cardiovascular death (adjusted hazard ratio (HR) 1.14, 95% CI, 1.03-1.27) and with a 14% greater risk of all-cause death (adjusted HR 1.14, 95% CI, 1.04 -1.26), while every 40% increase of delta hs- CRP (baseline to 6 months) was associated with a 9% greater risk of the composite end point (adjusted HR 1.09, 95% CI, 1.02-1.17) and a 10% greater risk of myocardial infarction (adjusted HR 1.10, 95%, CI 1.00 -1.20). CONCLUSIONS: Temporal changes in NT-proBNP and hs-CRP are quantitatively associated with future cardiovascular events, supporting their role in dynamic risk stratification of NSTEACS.
  •  
45.
  • Choi, Y S, et al. (author)
  • Fast antenna selection algorithms for MIMO systems
  • 2003
  • In: IEEE 58th Vehicular Technology Conference, 2003. VTC 2003-Fall.. - 1090-3038. - 0780379543 ; 3, s. 1733-1737
  • Conference paper (peer-reviewed)abstract
    • We consider the capacity of multiple-input-multiple-output (MIMO) systems with reduced complexity. One link end uses all available antennas, while the other chooses the "best" L out of N antennas. The selection of the optimum antenna subset requires an exhaustive search of all possible combinations, involving (/sub L//sup N/) computations of determinants of size L /spl times/ L, which can become prohibitively complex. In this paper, we suggest a class of fast antenna selection algorithm that are based on the correlation or mutual information between the signals at the different antenna elements. It requires less than N/sup 2/ vector multiplications and thus leads to dramatic savings on the computation time. Its performance is very close to the optimum selection procedure: the capacity penalty is less than l bit/s/Hz for the analyzed examples. The algorithm thus offers the possibility of almost-optimum selection even in fast-changing environments.
  •  
46.
  • Derigs, Dominik, et al. (author)
  • A novel averaging technique for discrete entropy-stable dissipation operators for ideal MHD
  • 2017
  • In: Journal of Computational Physics. - : Elsevier. - 0021-9991 .- 1090-2716. ; 330, s. 624-632
  • Journal article (peer-reviewed)abstract
    • Entropy stable schemes can be constructed with a specific choice of the numerical flux function. First, an entropy conserving flux is constructed. Secondly, an entropy stable dissipation term is added to this flux to guarantee dissipation of the discrete entropy. Present works in the field of entropy stable numerical schemes are concerned with thorough derivations of entropy conservative fluxes for ideal MHD. However, as we show in this work, if the dissipation operator is not constructed in a very specific way, it cannot lead to a generally stable numerical scheme. The two main findings presented in this paper are that the entropy conserving flux of Ismail & Roe can easily break down for certain initial conditions commonly found in astrophysical simulations, and that special care must be taken in the derivation of a discrete dissipation matrix for an entropy stable numerical scheme to be robust. We present a convenient novel averaging procedure to evaluate the entropy Jacobians of the ideal MHD and the compressible Euler equations that yields a discretization with favorable robustness properties.
  •  
47.
  • Derigs, Dominik, et al. (author)
  • A novel high-order, entropy stable, 3D AMR MHD solver with guaranteed positive pressure
  • 2016
  • In: Journal of Computational Physics. - : Elsevier. - 0021-9991 .- 1090-2716. ; 317, s. 223-256
  • Journal article (peer-reviewed)abstract
    • We describe a high-order numerical magnetohydrodynamics (MHD) solver built upon a novel non-linear entropy stable numerical flux function that supports eight travelling wave solutions. By construction the solver conserves mass, momentum, and energy and is entropy stable. The method is designed to treat the divergence-free constraint on the magnetic field in a similar fashion to a hyperbolic divergence cleaning technique. The solver described herein is especially well-suited for flows involving strong discontinuities. Furthermore, we present a new formulation to guarantee positivity of the pressure. We present the underlying theory and implementation of the new solver into the multi-physics, multi-scale adaptive mesh refinement (AMR) simulation code FLASH (http://flash.uchicago.edu). The accuracy, robustness and computational efficiency is demonstrated with a number of tests, including comparisons to available MHD implementations in FLASH.
  •  
48.
  • Derigs, Dominik, et al. (author)
  • Entropy Stable Finite Volume Approximations for Ideal Magnetohydrodynamics
  • 2018
  • In: Jahresbericht der Deutschen Mathematiker-Vereinigung (Teubner). - : Springer Berlin/Heidelberg. - 0012-0456 .- 1869-7135. ; 120:3, s. 153-219
  • Journal article (peer-reviewed)abstract
    • This article serves as a summary outlining the mathematical entropy analysis of the ideal magnetohydrodynamic (MHD) equations. We select the ideal MHD equations as they are particularly useful for mathematically modeling a wide variety of magnetized fluids. In order to be self-contained we first motivate the physical properties of a magnetic fluid and how it should behave under the laws of thermodynamics. Next, we introduce a mathematical model built from hyperbolic partial differential equations (PDEs) that translate physical laws into mathematical equations. After an overview of the continuous analysis, we thoroughly describe the derivation of a numerical approximation of the ideal MHD system that remains consistent to the continuous thermodynamic principles. The derivation of the method and the theorems contained within serve as the bulk of the review article. We demonstrate that the derived numerical approximation retains the correct entropic properties of the continuous model and show its applicability to a variety of standard numerical test cases for MHD schemes. We close with our conclusions and a brief discussion on future work in the area of entropy consistent numerical methods and the modeling of plasmas.
  •  
49.
  • Derigs, Dominik, et al. (author)
  • Ideal GLM-MHD : About the entropy consistent nine-wave magnetic field divergence diminishing ideal magnetohydrodynamics equations
  • 2018
  • In: Journal of Computational Physics. - : Elsevier. - 0021-9991 .- 1090-2716. ; 364, s. 420-467
  • Journal article (peer-reviewed)abstract
    • The paper presents two contributions in the context of the numerical simulation of magnetized fluid dynamics. First, we show how to extend the ideal magnetohydrodynamics (MHD) equations with an inbuilt magnetic field divergence cleaning mechanism in such a way that the resulting model is consistent with the second law of thermodynamics. As a byproduct of these derivations, we show that not all of the commonly used divergence cleaning extensions of the ideal MHD equations are thermodynamically consistent. Secondly, we present a numerical scheme obtained by constructing a specific finite volume discretization that is consistent with the discrete thermodynamic entropy. It includes a mechanism to control the discrete divergence error of the magnetic field by construction and is Galilean invariant. We implement the new high-order MHD solver in the adaptive mesh refinement code FLASH where we compare the divergence cleaning efficiency to the constrained transport solver available in FLASH (unsplit staggered mesh scheme).
  •  
50.
  • Erlinge, David, et al. (author)
  • Clopidogrel metaboliser status based on point-of-care CYP2C19 genetic testing in patients with coronary artery disease
  • 2014
  • In: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 111:5, s. 943-950
  • Journal article (peer-reviewed)abstract
    • We compared results obtained with the Nanosphere Verigene (R) System, a novel point-of-care (POC) genetic test capable of analysing 11, CYP2C19 variants within 3 hours, to an established, validated genotyping method (Affymetrix (TM) DMET+; reference assay) for identifying extensive and reduced metabolisers of clopidogrel. Based on genotyping, patients (N=82) with stable coronary artery disease on clopidogrel 75 mg daily were defined as extensive metabolisers (*1/*1, *1/*17,*17/*17), reduced metabolisers (*1/*2,*1/*8,*2/*2,*2/*3), or of indeterminate metaboliser status (*2/*17). Pharmacokinetic exposure to clopidogrel's active metabolite and pharmacodynamic measures with P2Y12 reaction units (PRU) (VerifyNow (R) P2Y12 assay), and VASP PRI (PRI) were also assessed. There was a 99.9% overall; concordance of marker-level data between the Nanosphere Verigene and DMET+ systems in identifying the CYP2C19 variants and 100% agreement in classifying the patients as extensive (n=59) or reduced metabolisers (n=15). Extensive metabolisers had significantly higher active metabolite exposure than reduced metabolisers (LS means 12.6 ng*h/ml vs 7.7 ng*h/ml; p<0.001). Extensive metabolisers also had lower PRU (LS means 158 vs 212; p=0.003) and VASP PRI (LS means 48% vs 63%, p=0.01) compared to reduced metabolisers. Rates of high on-treatment platelet reactivity were higher in reduced metabolisers compared to extensive metabolisers (VASP PRI >= 50%: 79% vs 47%; PRU >235: 33% vs 16%). The Nanosphere Verigene CBS system identified 11 CYP2C19 alleles in less than 3 hours with a high degree of accuracy when compared to a conventional method, and was further validated against pharmacokinetic and pharmacodynamic phenotypes.
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